tbuckley/cabot-search huggingface dataset:
Normative Echocardiographic Left Ventricular Parameters and Reference Intervals in Infants
Authors: R. Ottilia B. Vøgg, Anne-Sophie Sillesen, Jan Wohlfahrt, Christian Pihl, Anna Axelsson Raja, Niels Vejlstrup, Jakob B. Norsk, Eleni Elia, Lynn A. Sleeper, Steven D. Colan, Kasper K. Iversen, Heather A. Boyd, Henning Bundgaard
Journal: Journal of the American College of Cardiology (2023)
Uptitrating Treatment After Heart Failure Hospitalization Across the Spectrum of Left Ventricular Ejection Fraction
Authors: Matteo Pagnesi, Marco Metra, Alain Cohen-Solal, Christopher Edwards, Marianna Adamo, Daniela Tomasoni, Carolyn S.P. Lam, Ovidiu Chioncel, Rafael Diaz, Gerasimos Filippatos, Piotr Ponikowski, Karen Sliwa, Adriaan A. Voors, Antoine Kimmoun, Maria Novosadova, Koji Takagi, Marianela Barros, Albertino Damasceno, Hadiza Saidu, Etienne Gayat, Peter S. Pang, Jelena Celutkiene, Gad Cotter, Alexandre Mebazaa, Beth Davison
Journal: Journal of the American College of Cardiology (2023)
Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation
Authors: Matthew J. Lewis, Leigh C. Reardon, Jamil Aboulhosn, Christiane Haeffele, Sharon Chen, Yuli Kim, Stephanie Fuller, Lisa Forbess, Laith Alshawabkeh, Marcus A. Urey, Wendy M. Book, Fred Rodriguez, Jonathan N. Menachem, Daniel E. Clark, Anne Marie Valente, Matthew Carazo, Alexander Egbe, Heidi M. Connolly, Eric V. Krieger, Jilian Angiulo, Ari Cedars, Jong Ko, Roni M. Jacobsen, Michael G. Earing, Jonathan W. Cramer, Peter Ermis, Christopher Broda, Natalia Nugaeva, Heather Ross, Jordan D. Awerbach, Richard A. Krasuski, Marlon Rosenbaum
Journal: Journal of the American College of Cardiology (2023)
Morbidity and Mortality in Adult Fontan Patients After Heart or Combined Heart-Liver Transplantation
Authors: Matthew J. Lewis, Leigh C. Reardon, Jamil Aboulhosn, Christiane Haeffele, Sharon Chen, Yuli Kim, Stephanie Fuller, Lisa Forbess, Laith Alshawabkeh, Marcus A. Urey, Wendy M. Book, Fred Rodriguez, Jonathan N. Menachem, Daniel E. Clark, Anne Marie Valente, Matthew Carazo, Alexander Egbe, Heidi M. Connolly, Eric V. Krieger, Jilian Angiulo, Ari Cedars, Jong Ko, Roni M. Jacobsen, Michael G. Earing, Jonathan W. Cramer, Peter Ermis, Christopher Broda, Natalia Nugaeva, Heather Ross, Jordan D. Awerbach, Richard A. Krasuski, Marlon Rosenbaum
Journal: Journal of the American College of Cardiology (2023)
Engineering cannabidiol synergistic carbon monoxide nanocomplexes to enhance cancer therapy via excessive autophagy
Authors: Chang Xiao, Yue Sun, Jialong Fan, William Nguyen, Simin Chen, Ying Long, Wei Chen, Aiguo Zhu, Bin Liu
Journal: Acta Pharmaceutica Sinica B (2023)

Although carbon monoxide (CO)-based treatments have demonstrated the high cancer efficacy by promoting mitochondrial damage and core-region penetrating ability, the efficiency was often compromised by protective autophagy (mitophagy). Herein, cannabidiol (CBD) is integrated into biomimetic carbon monoxide nanocomplexes ([email protected]) to address this issue by inducing excessive autophagy. The biomimetic membrane not only prevents premature drugs leakage, but also prolongs blood circulation for tumor enrichment. After entering the acidic tumor microenvironment, carbon monoxide (CO) donors are stimulated by hydrogen oxide (H2O2) to disintegrate into CO and Mn2+. The comprehensive effect of CO/Mn2+ and CBD can induce ROS-mediated cell apoptosis. In addition, [email protected] excessive autophagy can promote cancer cell death by increasing autophagic flux via class III PI3K/BECN1 complex activation and blocking autolysosome degradation via LAMP1 downregulation. Furthermore, in vivo experiments showed that [email protected]+ laser strongly inhibited tumor growth and attenuated liver and lung metastases by downregulating VEGF and MMP9 proteins. This strategy may highlight the pro-death role of excessive autophagy in TNBC treatment, providing a novel yet versatile avenue to enhance the efficacy of CO treatments. Importantly, this work also indicated the applicability of CBD for triple-negative breast cancer (TNBC) therapy through excessive autophagy.
RANKL+ senescent cells under mechanical stress: a therapeutic target for orthodontic root resorption using senolytics
Authors: Yue Zhou, Aki Nishiura, Hidetoshi Morikuni, Wenqi Deng, Toru Tsujibayashi, Yoshihiro Momota, Yuki Azetsu, Masamichi Takami, Yoshitomo Honda, Naoyuki Matsumoto
Journal: International Journal of Oral Science (2023)

Abstract In dentistry, orthodontic root resorption is a long-lasting issue with no effective treatment strategy, and its mechanisms, especially those related to senescent cells, remain largely unknown. Here, we used an orthodontic intrusion tooth movement model with an L-loop in rats to demonstrate that mechanical stress-induced senescent cells aggravate apical root resorption, which was prevented by administering senolytics (a dasatinib and quercetin cocktail). Our results indicated that cementoblasts and periodontal ligament cells underwent cellular senescence (p21 + or p16 + ) and strongly expressed receptor activator of nuclear factor-kappa B (RANKL) from day three, subsequently inducing tartrate-resistant acid phosphatase (TRAP)-positive odontoclasts and provoking apical root resorption. More p21 + senescent cells expressed RANKL than p16 + senescent cells. We observed only minor changes in the number of RANKL + non-senescent cells, whereas RANKL + senescent cells markedly increased from day seven. Intriguingly, we also found cathepsin K + p21 + p16 + cells in the root resorption fossa, suggesting senescent odontoclasts. Oral administration of dasatinib and quercetin markedly reduced these senescent cells and TRAP + cells, eventually alleviating root resorption. Altogether, these results unveil those aberrant stimuli in orthodontic intrusive tooth movement induced RANKL + early senescent cells, which have a pivotal role in odontoclastogenesis and subsequent root resorption. These findings offer a new therapeutic target to prevent root resorption during orthodontic tooth movement.
Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease
Authors: Bruna Bellaver, Guilherme Povala, Pamela C. L. Ferreira, João Pedro Ferrari-Souza, Douglas T. Leffa, Firoza Z. Lussier, Andréa L. Benedet, Nicholas J. Ashton, Gallen Triana-Baltzer, Hartmuth C. Kolb, Cécile Tissot, Joseph Therriault, Stijn Servaes, Jenna Stevenson, Nesrine Rahmouni, Oscar L. Lopez, Dana L. Tudorascu, Victor L. Villemagne, Milos D. Ikonomovic, Serge Gauthier, Eduardo R. Zimmer, Henrik Zetterberg, Kaj Blennow, Howard J. Aizenstein, William E. Klunk, Beth E. Snitz, Pauline Maki, Rebecca C. Thurston, Ann D. Cohen, Mary Ganguli, Thomas K. Karikari, Pedro Rosa-Neto, Tharick A. Pascoal
Journal: Nature Medicine (2023)

Abstract An unresolved question for the understanding of Alzheimer’s disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts ( n = 1,016), we tested whether astrocyte reactivity modulates the association of Aβ with tau phosphorylation in CU individuals. We found that Aβ was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast + ). Cross-sectional and longitudinal tau–positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of Aβ only in CU Ast + individuals. Our findings suggest astrocyte reactivity as an important upstream event linking Aβ with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials.
Prosodic signatures of ASD severity and developmental delay in preschoolers
Authors: Michel Godel, François Robain, Fiona Journal, Nada Kojovic, Kenza Latrèche, Ghislaine Dehaene-Lambertz, Marie Schaer
Journal: npj Digital Medicine (2023)

Atypical prosody in speech production is a core feature of Autism Spectrum Disorder (ASD) that can impact everyday life communication. Because the ability to modulate prosody develops around the age of speech acquisition, it might be affected by ASD symptoms and developmental delays that emerge at the same period. Here, we investigated the existence of a prosodic signature of developmental level and ASD symptom severity in a sample of 74 autistic preschoolers. We first developed an original diarization pipeline to extract preschoolers' vocalizations from recordings of naturalistic social interactions. Using this novel approach, we then found a robust voice quality signature of ASD developmental difficulties in preschoolers. Furthermore, some prosodic measures were associated with one year later outcome in participants who had not acquired speech yet. Altogether, our results highlight the potential benefits of automatized diarization algorithms and prosodic metrics for digital phenotyping in psychiatry, helping clinicians establish early diagnosis and prognosis.
Management of regional citrate anticoagulation for continuous renal replacement therapy: guideline recommendations from Chinese emergency medical doctor consensus
Authors: Shu-Yuan Liu, Sheng-Yong Xu, Lu Yin, Ting Yang, Kui Jin, Qiu-Bin Zhang, Feng Sun, Ding-Yu Tan, Tian-Yu Xin, Yu-Guo Chen, Xiao-Dong Zhao, Xue-Zhong Yu, Jun Xu, Xu-Feng Chen, Zhi Chen, Qing-Li Dou, Jian Guan, Yao-Song Gui, Zhong-Wei Huang, Xiao-Min Li, Dan-Ping Liu, Jing-Jun Lv, Yong Liu, Chuan-Yun Qian, Yi Shan, Yan Shi, Ming Sun, Hai-Ying Wu, Jian Xia, Feng Xu, Tie Xu, Xian-Liang Yan, Jian-Zhong Yang, Yong-Wu Yu, Jin-Song Zhang, Mao Zhang, Wei Zhang, Hong-Yu Zhao, Dong-Hui Zheng, Ping Zhou, Bao-Feng Zhu, Hua-Dong Zhu, Shi-Qian Shen, John Prowle, Martin Bellgardt
Journal: Military Medical Research (2023)

Continuous renal replacement therapy (CRRT) is widely used for treating critically-ill patients in the emergency department in China. Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT. Regional citrate anticoagulation (RCA) has been shown to potentially be safer and more effective and is now recommended as the preferred anticoagulant method for CRRT. However, there is still a lack of unified standards for RCA management in the world, and there are many problems in using this method in clinical practice. The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association (CMDA) organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues, including the advantages and disadvantages of RCA in CRRT anticoagulation, the principle of RCA, parameter settings for RCA, monitoring of RCA (mainly metabolic acid-base disorders), and special issues during RCA. Based on the latest available research evidence as well as the paneled experts' clinical experience, considering the generalizability, suitability, and potential resource utilization, while also balancing clinical advantages and disadvantages, a total of 16 guideline recommendations were formed from the experts' consensus.
Envisioning environmental equity: climate change, health, and racial justice
Authors: Thilagawathi Abi Deivanayagam, Sonora English, Jason Hickel, Jon Bonifacio, Renzo R Guinto, Kyle X Hill, Mita Huq, Rita Issa, Hans Mulindwa, Heizal Patricia Nagginda, Priscila de Morais Sato, Sujitha Selvarajah, Chetna Sharma, Delan Devakumar
Journal: The Lancet (2023)

Climate change has a broad range of health impacts and tackling climate change could be the greatest opportunity for improving global health this century. Yet conversations on climate change and health are often incomplete, giving little attention to structural discrimination and the need for racial justice. Racism kills, and climate change kills. Together, racism and climate change interact and have disproportionate effects on the lives of minoritised people both within countries and between the Global North and the Global South. This paper has three main aims. First, to survey the literature on the unequal health impacts of climate change due to racism, xenophobia, and discrimination through a scoping review. We found that racially minoritised groups, migrants, and Indigenous communities face a disproportionate burden of illness and mortality due to climate change in different contexts. Second, this paper aims to highlight inequalities in responsibility for climate change and the effects thereof. A geographical visualisation of responsibility for climate change and projected mortality and disease risk attributable to climate change per 100 000 people in 2050 was conducted. These maps visualise the disproportionate burden of illness and mortality due to climate change faced by the Global South. Our third aim is to highlight the pathways through which climate change, discrimination, and health interact in most affected areas. Case studies, testimony, and policy analysis drawn from multidisciplinary perspectives are presented throughout the paper to elucidate these pathways. The health community must urgently examine and repair the structural discrimination that drives the unequal impacts of climate change to achieve rapid and equitable action.
Human microglia show unique transcriptional changes in Alzheimer’s disease
Authors: Katherine E. Prater, Kevin J. Green, Sainath Mamde, Wei Sun, Alexandra Cochoit, Carole L. Smith, Kenneth L. Chiou, Laura Heath, Shannon E. Rose, Jesse Wiley, C. Dirk Keene, Ronald Y. Kwon, Noah Snyder-Mackler, Elizabeth E. Blue, Benjamin Logsdon, Jessica E. Young, Ali Shojaie, Gwenn A. Garden, Suman Jayadev
Journal: Nature Aging (2023)

Abstract Microglia, the innate immune cells of the brain, influence Alzheimer’s disease (AD) progression and are potential therapeutic targets. However, microglia exhibit diverse functions, the regulation of which is not fully understood, complicating therapeutics development. To better define the transcriptomic phenotypes and gene regulatory networks associated with AD, we enriched for microglia nuclei from 12 AD and 10 control human dorsolateral prefrontal cortices (7 males and 15 females, all aged &gt;60 years) before single-nucleus RNA sequencing. Here we describe both established and previously unrecognized microglial molecular phenotypes, the inferred gene networks driving observed transcriptomic change, and apply trajectory analysis to reveal the putative relationships between microglial phenotypes. We identify microglial phenotypes more prevalent in AD cases compared with controls. Further, we describe the heterogeneity in microglia subclusters expressing homeostatic markers. Our study demonstrates that deep profiling of microglia in human AD brain can provide insight into microglial transcriptional changes associated with AD.
Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation
Authors: David Adlam, Takiy-Eddine Berrandou, Adrien Georges, Christopher P. Nelson, Eleni Giannoulatou, Joséphine Henry, Lijiang Ma, Montgomery Blencowe, Tamiel N. Turley, Min-Lee Yang, Sandesh Chopade, Chris Finan, Peter S. Braund, Ines Sadeg-Sayoud, Siiri E. Iismaa, Matthew L. Kosel, Xiang Zhou, Stephen E. Hamby, Jenny Cheng, Lu Liu, Ingrid Tarr, David W. M. Muller, Valentina d’Escamard, Annette King, Liam R. Brunham, Ania A. Baranowska-Clarke, Stéphanie Debette, Philippe Amouyel, Jeffrey W. Olin, Snehal Patil, Stephanie E. Hesselson, Keerat Junday, Stavroula Kanoni, Krishna G. Aragam, Adam S. Butterworth, Mark K. Bakker, Ynte M. Ruigrok, Marysia S. Tweet, Rajiv Gulati, Nicolas Combaret, Daniella Kadian-Dodov, Jonathan M. Kalman, Diane Fatkin, Aroon D. Hingorani, Jacqueline Saw, Tom R. Webb, Sharonne N. Hayes, Xia Yang, Santhi K. Ganesh, Timothy M. Olson, Jason C. Kovacic, Robert M. Graham, Nilesh J. Samani, Nabila Bouatia-Naji
Journal: Nature Genetics (2023)

Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.
Robust and prototypical immune responses toward COVID-19 vaccine in First Nations peoples are impacted by comorbidities
Authors: Wuji Zhang, Lukasz Kedzierski, Brendon Y. Chua, Mark Mayo, Claire Lonzi, Vanessa Rigas, Bianca F. Middleton, Hayley A. McQuilten, Louise C. Rowntree, Lilith F. Allen, Ruth A. Purcell, Hyon-Xhi Tan, Jan Petersen, Priyanka Chaurasia, Francesca Mordant, Mikhail V. Pogorelyy, Anastasia A. Minervina, Jeremy Chase Crawford, Griffith B. Perkins, Eva Zhang, Stephanie Gras, E. Bridie Clemens, Jennifer A. Juno, Jennifer Audsley, David S. Khoury, Natasha E. Holmes, Irani Thevarajan, Kanta Subbarao, Florian Krammer, Allen C. Cheng, Miles P. Davenport, Branka Grubor-Bauk, P. Toby Coates, Britt Christensen, Paul G. Thomas, Adam K. Wheatley, Stephen J. Kent, Jamie Rossjohn, Amy W. Chung, John Boffa, Adrian Miller, Sarah Lynar, Jane Nelson, Thi H. O. Nguyen, Jane Davies, Katherine Kedzierska
Journal: Nature Immunology (2023)

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4+ and CD8+ T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people.
Targets and cross-reactivity of human T cell recognition of common cold coronaviruses
Authors: Alison Tarke, Yun Zhang, Nils Methot, Tara M. Narowski, Elizabeth Phillips, Simon Mallal, April Frazier, Gilberto Filaci, Daniela Weiskopf, Jennifer M. Dan, Lakshmanane Premkumar, Richard H. Scheuermann, Alessandro Sette, Alba Grifoni
Journal: Cell Reports Medicine (2023)

The coronavirus (CoV) family includes several viruses infecting humans, highlighting the importance of exploring pan-CoV vaccine strategies to provide broad adaptive immune protection. We analyze T cell reactivity against representative Alpha (NL63) and Beta (OC43) common cold CoVs (CCCs) in pre-pandemic samples. S, N, M, and nsp3 antigens are immunodominant, as shown for severe acute respiratory syndrome 2 (SARS2), while nsp2 and nsp12 are Alpha or Beta specific. We further identify 78 OC43- and 87 NL63-specific epitopes, and, for a subset of those, we assess the T cell capability to cross-recognize sequences from representative viruses belonging to AlphaCoV, sarbecoCoV, and Beta-non-sarbecoCoV groups. We find T cell cross-reactivity within the Alpha and Beta groups, in 89% of the instances associated with sequence conservation >67%. However, despite conservation, limited cross-reactivity is observed for sarbecoCoV, indicating that previous CoV exposure is a contributing factor in determining cross-reactivity. Overall, these results provide critical insights in developing future pan-CoV vaccines.
Postsynaptic synucleins mediate endocannabinoid signaling
Authors: Eddy Albarran, Yue Sun, Yu Liu, Karthik Raju, Ao Dong, Yulong Li, Sui Wang, Thomas C. Südhof, Jun B. Ding
Journal: Nature Neuroscience (2023)

Abstract Endocannabinoids are among the most powerful modulators of synaptic transmission throughout the nervous system, and yet little is understood about the release of endocannabinoids from postsynaptic compartments. Here we report an unexpected finding that endocannabinoid release requires synucleins, key contributors to Parkinson’s disease. We show that endocannabinoids are released postsynaptically by a synuclein-dependent and SNARE-dependent mechanism. Specifically, we found that synuclein deletion blocks endocannabinoid-dependent synaptic plasticity; this block is reversed by postsynaptic expression of wild-type but not of mutant α-synuclein. Whole-cell recordings and direct optical monitoring of endocannabinoid signaling suggest that the synuclein deletion specifically blocks endocannabinoid release. Given the presynaptic role of synucleins in regulating vesicle lifecycle, we hypothesize that endocannabinoids are released via a membrane interaction mechanism. Consistent with this hypothesis, postsynaptic expression of tetanus toxin light chain, which cleaves synaptobrevin SNAREs, also blocks endocannabinoid-dependent signaling. The unexpected finding that endocannabinoids are released via a synuclein-dependent mechanism is consistent with a general function of synucleins in membrane trafficking and adds a piece to the longstanding puzzle of how neurons release endocannabinoids to induce synaptic plasticity.
Seeding the aggregation of TDP-43 requires post-fibrillization proteolytic cleavage
Authors: Senthil T. Kumar, Sergey Nazarov, Sílvia Porta, Niran Maharjan, Urszula Cendrowska, Malek Kabani, Francesco Finamore, Yan Xu, Virginia M.-Y. Lee, Hilal A. Lashuel
Journal: Nature Neuroscience (2023)

Abstract Despite the strong evidence linking the transactive response DNA-binding protein 43 (TDP-43) aggregation to the pathogenesis of frontotemporal lobar degeneration with TDP-43, amyotrophic lateral sclerosis and several neurodegenerative diseases, our knowledge of the sequence and structural determinants of its aggregation and neurotoxicity remains incomplete. Herein, we present a new method for producing recombinant full-length TDP-43 filaments that exhibit sequence and morphological features similar to those of brain-derived TDP-43 filaments. We show that TDP-43 filaments contain a β-sheet-rich helical amyloid core that is fully buried by the flanking structured domains of the protein. We demonstrate that the proteolytic cleavage of TDP-43 filaments and exposure of this amyloid core are necessary for propagating TDP-43 pathology and enhancing the seeding of brain-derived TDP-43 aggregates. Only TDP-43 filaments with exposed amyloid core efficiently seeded the aggregation of endogenous TDP-43 in cells. These findings suggest that inhibiting the enzymes mediating cleavage of TDP-43 aggregates represents a viable disease-modifying strategy to slow the progression of amyotrophic lateral sclerosis and other TDP-43 proteinopathies.